The occurrence of obesity in adults as well as children has rapidly increased over the last ten years, which has raised the risk of associated health problems including Type 2 diabetes, heart diseases, cancer, hypertension. Accordingly, many studies for obesity treatment have been performed.
Melanine-concentrating hormone (MCH) is a cyclic 19 amino acid peptide that has been implicated to be involved in the regulation of feeding behavior of a mammal. Studies with MCH-administered rat models have shown an increase in food intake, while MCH-deficient mice undergo weight loss due to a significant decrease in the food intake and an increase in the metabolic rate (see D. Qu et al., Nature, 380 (6571), 243-247, 1996). Also, the effect of MCH in regulating the feeding behavior is known to be attributed to MCH receptor-1 which stimulates feeding, and obesity in MCH receptor-1 knock-out mice does not take place even after MCH administration (see A. L. Handlon and H. Zhou, J. Med. Chem. 49, 4017-4022, 2006).
Meanwhile, the effect of MCH is mediated by an MCH receptor-1 antagonist which is one of G-protein-coupled receptors. Such a MCH receptor-1 antagonist is also reported to be useful in treating depression and anxiety (see B. Borowsky et al., Nature Medicine, 8(8), 825-830, 2002), and also diabetes and metabolic disturbance (see D. S. Ludwig et al., J. Clin. Invest. 107, 379-386, 2001).
A specific MCH receptor-1 antagonist, GW3430, developed by Amgen and GlaxoSmithKline is currently undergoing clinical evaluation for the treatment of obesity (see Dyck et al, Bioorg. Med. Chem, Lett. 2006, 16, 4237-4242).
Also, Xenical® and Reductil®, the structures of which are shown below, are marketed as drugs for obesity treatment. However, they show unsatisfactory therapeutic effects and cause undesirable side effects (see Trisha Gura, Science 2003, 299, 849-852).

Accordingly, the present inventors have endeavored to develop a novel MCH receptor-1 antagonist and found that an imidazole derivative having a specific structure is capable of acting as an effective MCH receptor-1 antagonist to be useful for preventing or treating MCH-related diseases including obesity.